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Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.


ABSTRACT:

Objective

We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.

Background

Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.

Method

In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.

Results

High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.

Conclusions

Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

SUBMITTER: Dreyer SB 

PROVIDER: S-EPMC7373491 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.

Dreyer Stephan B SB   Pinese Mark M   Jamieson Nigel B NB   Scarlett Christopher J CJ   Colvin Emily K EK   Pajic Marina M   Johns Amber L AL   Humphris Jeremy L JL   Wu Jianmin J   Cowley Mark J MJ   Chou Angela A   Nagrial Adnan M AM   Chantrill Lorraine L   Chin Venessa T VT   Jones Marc D MD   Moran-Jones Kim K   Carter Christopher Ross CR   Dickson Euan J EJ   Samra Jaswinder S JS   Merrett Neil D ND   Gill Anthony J AJ   Kench James G JG   Duthie Fraser F   Miller David K DK   Cooke Susanna S   Aust Daniela D   Knösel Thomas T   Rümmele Petra P   Grützmann Robert R   Pilarsky Christian C   Nguyen Nam Q NQ   Musgrove Elizabeth A EA   Bailey Peter J PJ   McKay Colin J CJ   Biankin Andrew V AV   Chang David K DK  

Annals of surgery 20200801 2


<h4>Objective</h4>We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.<h4>Background</h4>Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival,  ...[more]

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